Cube Biotech and X-Chem Breakthrough Enables DNA-Encoded Library Screening of Membrane Proteins
Key Insights
Cube Biotech (search) and X-Chem (search) successfully completed Project DEL-MP, demonstrating that copolymer-stabilized membrane proteins are suitable for DNA-Encoded Library screening and open new possibilities for challenging drug targets.
The collaboration combined Cube Biotech (search)'s NativeMP™ copolymer technology with X-Chem (search)'s DEL platform, proving that high-quality, data-driven discovery is now possible for membrane protein targets that were previously difficult to screen effectively.
Benchmark testing of NativeMP™ proteins including GLP1R (search), EGFR (search), TNF (search), P2YR11 (search) and P2X4 (search) revealed highly productive DEL screen readouts with enriched, target-selective compounds suitable for further development.
Cube Biotech (search) and X-Chem (search) have announced the successful completion of Project DEL-MP, a groundbreaking collaboration that demonstrates DNA-Encoded Library (DEL) screening can be effectively applied to membrane proteins—some of the most challenging targets in drug discovery. The partnership combines Cube Biotech's proprietary NativeMP™ copolymer technology with X-Chem's world-class DEL platform to unlock new possibilities for drug discovery against previously intractable targets.
Revolutionary Approach to Membrane Protein Screening
The collaborative initiative proved that copolymer-stabilized membrane proteins are not only suitable for DEL screening but also open up completely new possibilities for even the most challenging targets. Cube Biotech (search)'s NativeMP™ technology enables the stabilization of functional membrane proteins in near-native conformations, while X-Chem (search) provides expertise in complex target screening through its DEL platform.
"For years, the field has questioned whether DEL screening could be extended to membrane proteins," said Barbara Maertens, COO and co-founder of Cube Biotech (search). "With Project DEL-MP, we've proven that not only is it possible—it's optimal. NativeMP™ preserves native conformation, protein functionality, and accessibility of extracellular pockets—a trifecta for meaningful hit discovery."
Validation Across Multiple Target Classes
Project DEL-MP served as a joint proof-of-concept and platform validation program with three key objectives: demonstrating robust DEL hit discovery against selected membrane protein targets from different classes stabilized in various NativeMP™ copolymers, benchmarking performance across target types, and establishing seamless automation compatibility for scalable screening workflows.
The benchmark testing revealed highly productive results across multiple membrane protein targets. NativeMP™ proteins, including GLP1R (search), EGFR (search), TNF (search), P2YR11 (search) and P2X4 (search), demonstrated enriched, target-selective compounds suitable for off-DNA synthesis and assays, independent of the type of NativeMP™ copolymers used for stabilization.
Addressing Long-Standing Drug Discovery Challenges
"Membrane proteins are some of the most important targets in drug discovery, yet they have been among the most difficult to screen effectively," said Matt Clark, CSO of X-Chem (search). "By combining Cube Biotech (search)'s NativeMP™ technology with X-Chem's DEL screening platform, we have shown that high-quality, data-driven discovery is now possible for these challenging targets."
Results from feasibility experiments conducted on X-Chem (search)'s screening platform showed promising outcomes for NativeMP™-stabilized membrane protein targets, maintaining binding competency and structural fidelity over extended incubation periods. The collaboration also demonstrated seamless automation compatibility for scalable DEL screening workflows using high-throughput instrumentation.
Expanding Therapeutic Possibilities
The breakthrough validates a new path forward that expands the impact of DEL technology and opens opportunities for innovation across many therapeutic areas. Cube Biotech (search)'s NativeMP™ copolymer technology enables native-like solubilization of even the most fragile targets—including GPCRs and multi-pass transporters—without the use of harsh detergents.
This advancement represents a significant step forward in making previously "undruggable" membrane protein targets accessible to systematic drug discovery efforts. The successful integration of these complementary technologies provides the pharmaceutical industry with new tools to tackle some of the most challenging targets in biomedical research, potentially leading to breakthrough therapeutics across multiple disease areas.